Long-Term Safety, Tolerability of Ralinepag in Pulmonary Arterial Hypertension

Long-term use of ralinepag for pulmonary arterial hypertension is safe and well-tolerated, with a risk-benefit ratio consistent with that found in the phase 2 clinical trial of ralinepag. This was among the results of an open-label extension study of ralinepag recently presented at the American Thoracic Society (ATS) 2022 International Conference, held in San Francisco, CA, May 13 to 18.

Ralinepag is a prostacyclin receptor agonist being studied in clinical trials for the treatment of World Health Organization (WHO) Group 1 pulmonary hypertension. Researchers sought to investigate long-term safety and tolerability of ralinepag in patients with PAH, with the secondary objective of assessing the effect of long-term ralinepag use on changes in 6-minute walk distance (6MWD), WHO Functional Class (FC), hemodynamics, and time to clinical worsening.

The investigators conducted a phase 2 open-label extension (OLE) study of ralinepag (ClinicalTrials.gov Identifier: NCT02279745) following the 22-week placebo-controlled parent study (ClinicalTrials.gov Identifier: NCT02279160). The OLE included 45 of the original 61 participants from the parent study (86.7% <65 years of age; 86.7% female; 93.3% White; 71.1% in WHO FC II at baseline). OLE participants spent a median of 153.4 weeks in treatment with oral ralinepag. Those already treated with ralinepag in the placebo-controlled parent study continued with the same dosage, while participants receiving placebo in the parent study began treatment with ralinepag in the OLE, receiving individualized dose titration. Researchers conducted clinical evaluations every 3 months, for a maximum of 36 months.

With respect to safety and tolerability, researchers found adverse events (AEs) in the OLE were consistent with the parent study and with the safety profile of prostacyclin therapies; the most commonly reported AEs were headache (64%), diarrhea (38%), and jaw pain (33%), with 11.1% of subjects discontinuing due to AEs.

With respect to the study’s secondary outcomes, investigators found improvements from OLE baseline in the 6MWD (3 months: 20.9 m;, 6 months: 17.6 m; 12 months: 28.5 m; 24 months: 41.0 m; and 36 months: 47.0 m); median pulmonary vascular resistance (PVR; ‑52.2 dyn.sec/cm⁵) and mean pulmonary arterial pressure (‑2.0 mm Hg). Notably, neither WHO FC nor time to clinical worsening showed relevant changes, said study authors.  

Overall, said the investigators, “PVR reductions reported for the ralinepag group in the parent study were maintained in the OLE, while subjects from the placebo group saw significant improvements once on active treatment in the OLE.” The investigators concluded that “The overall safety profile of ralinepag was similar to that reported in the parent study and data from the OLE study demonstrate the benefit-risk ratio of ralinepag remains unchanged and positive.”

Reference

Klings ES, Barbera JA, Grover R, et al. Long-term data from Study APD811-007, an open-label extension study evaluating ralinepag for the treatment of pulmonary arterial hypertension. Presented at: the American Thoracic Society (ATS) 2022 International Conference; May 13-18, 2022; San Francisco, CA. Session A96.